Biomarker for Diagnosis and Monitoring of Treatment Response in Major Depressive Disorder: Changes in Serum L‐Glutamine Levels

Major depressive disorder (MDD) is a mood disorder that causes serious functional impairment. Existing diagnostic methods rely on subjective assessments because of its complex and heterogeneous pathophysiology; therefore, development of objective biomarkers is urgently needed. To control the high heterogeneity of MDD, a pairwise design in which depressed and remitted states of the same patient were paired to minimize the influence of intrinsic factors was introduced, and serum metabolite changes between states were analyzed using non-targeted and targeted metabolomics approaches. State-based biomarkers that could be used for objective diagnosis of MDD were identified, and their clinical applicability was validated in an expanded study group. L-Glutamine was selected because it showed a tendency to increase during the remitted state. Through multiple reaction monitoring-based quantitative verification, L-glutamine levels significantly increased in the remitted state compared with those in the depressed state, regardless of the influence of drug treatment, proving its potential as a diagnostic marker. This study identified differences in serum metabolites in patients with MDD using a metabolomic approach; L-glutamine could be used as a promising biomarker to distinguish between depressive and remissive states. These results can contribute to the precise diagnosis of MDD and establishment of personalized treatment strategies.